Cooperative Ligand Research Articles

Palladium mono-N-protected amino acid complexes: experimental validation of the ligand cooperation model in C-H activation.

Mechanistic proposals for the C-H activation reaction enabled by mono-N-protected amino acid ligands (MPAAs) have been supported by DFT calculations. The direct experimental observation of the ligand-assisted C-H activation has not yet been reported due to the lack of well-defined isolated palladium complexes with MPAAs that can serve as models. In this work, palladium complexes bearing chelating MPAAs (NBu4)[Pd(κ2-N,O-AcN-CHR-COO)(C6F5)py] (Ac = MeC(O); R = H, Me) and [Pd(κ2-N,O-MeNH-CH2-COO)(C6F5)py] have been isolated and characterized. Their evolution in a solution containing toluene leads to the C-H activation of the arene and the formation of the C6F5-C6H4Me coupling products. This process takes place only for the ligands with an acyl protecting group, showing the cooperating role of this group in a complex with a chelating MPAA, therefore experimentally validating this working model. The carboxylate group is inefficient in this C-H activation.

α-Methylation of Ketones and Indoles Catalyzed by a Manganese(I) PCNHCP Pincer Complex with Methanol as a C1 Source

Acceptorless alcohol dehydrogenation is a powerful reaction in sustainable synthesis. When combined in a tandem reaction with dehydrogenative coupling or hydrogen borrowing, acceptorless dehydrogenation can be used for the environmentally benign construction of C–C, C–N, and C–O bonds. While many of these reactions rely on using precious metals, in the past decade the use of earth-abundant metals has become more prevalent. If a green and renewable feedstock could be introduced as well, the sustainability of the acceptorless dehydrogenation could further be increased. Methanol would be such a substrate and could serve as a renewable C1 source when used for the methylation of a wide variety of substrates. Herein, we report the efficient manganese-catalyzed α-methylation of ketones and indoles. The manganese catalyst is based on a PCNHCP pincer platform containing a rare central carbene donor. The reaction supports a diverse set of functional groups, occurs at moderate temperatures (110 °C), and provides the corresponding methylated ketones and indoles in excellent yields. In contrast to previously reported mechanisms, the herein reported mechanism does not depend on metal–ligand cooperativity but rather proceeds via (i) a metal-based mechanism featuring a manganese hydride or (ii) via a ligand-centered mechanism where a manganese-carbonyl acts as catalytic center, depending on the used additive.

Metal–Ligand Cooperative Effect on Intramolecular Electron Transfer in Macrocycle-Encircled Copper–Oxygen Species

Metal–Ligand Cooperative Effect on Intramolecular Electron Transfer in Macrocycle-Encircled Copper–Oxygen Species

In Situ Imaging and Computational Modeling Reveal That Thiophene Complexation with Co(II)porphyrin/Graphite Is Highly Cooperative

Scanning tunneling microscopy (STM) was employed to quantitively investigate in situ binding of 3-phenyl thiophene (PhTh) to Co(II)octaethyl porphyrin (CoOEP) supported on highly ordered pyrolytic graphite (HOPG) in fluid solution. To our knowledge, this is the first single-molecule level study of a complexation reaction between a metalloporphyrin and a sulfur base at the solution/solid interface and one of the few examples of thiophene coordination with a d7 transition metal. Real-time imaging experiments revealed that PhTh binds reversibly to HOPG-supported CoOEP at room temperature. The coordination process increases with increasing PhTh concentration. The nearest-neighbor analysis of STM images indicates that the complexation reaction is cooperative. Because PhTh does not bind to CoOEP in solution, the STM results strongly suggest that the presence of HOPG is crucial to observe ligand binding and cooperativity in this system. Periodic plane-wave density functional theory (DFT) computations corroborate that PhTh has low binding affinity toward CoOEP in solution but predict that the ligand can adsorb to CoOEP/HOPG through coordination with S atoms or interact through noncovalent π–π bonding with the porphyrin chromophore. Three possible structures were considered, and DFT theory was used to calculate binding energies and free energies. In solution and on the HOPG surface both a π–π configuration and a η1(S) configuration have similar computed energies. The η1(S) structure shows the largest stabilization in going from the vapor to adsorbed on HOPG. We also show that statistical analysis of nearest neighbors is more sensitive to cooperative binding than is fitting with the Temkin or Langmuir isotherm. The implication is that isotherm fitting alone is insufficient for identifying cooperative binding on surfaces.

Structural Basis of Sequential and Concerted Cooperativity.

Allostery is a property of biological macromolecules featuring cooperative ligand binding and regulation of ligand affinity by effectors. The definition was introduced by Monod and Jacob in 1963, and formally developed as the "concerted model" by Monod, Wyman, and Changeux in 1965. Since its inception, this model of cooperativity was seen as distinct from and not reducible to the "sequential model" originally formulated by Pauling in 1935, which was developed further by Koshland, Nemethy, and Filmer in 1966. However, it is difficult to decide which model is more appropriate from equilibrium or kinetics measurements alone. In this paper, we examine several cooperative proteins whose functional behavior, whether sequential or concerted, is established, and offer a combined approach based on functional and structural analysis. We find that isologous, mostly helical interfaces are common in cooperative proteins regardless of their mechanism. On the other hand, the relative contribution of tertiary and quaternary structural changes, as well as the asymmetry in the liganded state, may help distinguish between the two mechanisms.

Ruthenium(II)-Catalyzed Hydrogenation and Tandem (De)Hydrogenation via Metal-Ligand Cooperation: Base- and Solvent-Assisted Switchable Selectivity.

A versatile, selective, solvent (methanol vs ethanol)- and base (potassium vs lithium carbonate)-assisted switchable synthesis of saturated ketone and α-methyl saturated ketone from α,β-unsaturated ketone is developed. Mechanistic aspects, evaluated from spectroscopic studies, in situ monitoring of the reaction progress, control studies, and labeling studies, further indicate the involvement of a tandem dehydrogenation-condensation-hydrogenation sequence in the reaction, in which the interconvertible coordination mode (imino N → Ru and amido N-Ru) of coordinated imidazole with Ru(II)-para-cymene is crucial, without which the efficiency and selectivity of the catalyst are completely lost. The catalyst demonstrates good efficiency, selectivity, and functional group tolerance and displays a broad scope (69 examples) for monomethylation and hydrogenation of unsaturated chalcones, double methylation of ketones, and N-methylation of amines.

Ligand cooperativity enables highly enantioselective C–C σ-bond hydroboration of cyclopropanes

<h2>Summary</h2> Given the utility of enantioenriched alkylboronates, asymmetric borylation has attracted substantial research interest in recent decades. Herein, a catalytic enantioselective hydroboration through desymmetrization of enantiotopic carbons in cyclopropanes involving C–C bond activation is reported. Treatment of cyclopropanes bearing an amide directing group in the presence of rhodium catalysis using HBpin as a boron source allows the construction of a series of alkyl boronates containing γ-stereogenic amines. The key to high enantioselectivity relies on two distinct ligands that act cooperatively: an exogenous monodentate chiral phosphite that induces enantioselectivity and an endogenous acetylacetonate that exerts a remarkably positive influence on the enhancement of enantioselectivity. Detailed experimental and computational studies elucidate the effect of ligand cooperativity and the key steps involving σ-bond activation process, C–B bond formation, and the absolute configuration of products.

Reversible Dioxygen Binding to Co(II) Complexes with Noninnocent Ligands.

A series of mononuclear Co(II) complexes with noninnocent (redox-active) ligands are prepared that exhibit metal-ligand cooperativity during the reversible binding of O2. The complexes have the general formula, [CoII(LS,N)(TpR2)] (R = Me, Ph), where LS,N is a bidentate o-aminothiophenolate and TpR2 is a hydrotris(pyrazol-1-yl)borate scorpionate with R-substituents at the 3- and 5-positions. Exposure to O2 at room temperature results in one-electron oxidation and deprotonation of LS,N. The oxidized derivatives possess substantial "singlet diradical" character arising from antiferromagnetic coupling between an iminothiosemiquinonate (ITSQ•-) ligand radical and a low-spin Co(II) ion. The [CoII(TpMe2)(X2ITSQ)] complexes, where X = H or tBu, coordinate O2 reversibly at reduced temperatures to provide Co/O2 adducts. The O2 binding reactions closely resemble those previously reported by our group (Kumar et al., J. Am. Chem. Soc. 2019,141, 10984-10987) for the related complexes [CoII(TpMe2)(tBu2SQ)] and [CoII(TpMe2)(tBu2ISQ)], where tBu2(I)SQ represents 4,6-di-tert-butyl-(2-imino)semiquinonate radicals. In each case, the oxygenation reaction proceeds via the addition of O2 to both the cobalt ion and the ligand radical, generating metallocyclic cobalt(III)-alkylperoxo structures. Thermodynamic measurements elucidate the relationship between O2 affinity and redox potentials of the (imino)(thio)semiquinonate radicals, as well as energetic differences between these reactions and conventional metal-based oxygenations. The results highlight the utility and versatility of noninnocent ligands in the design of O2-absorbing compounds.

Magnesium Pincer Complexes and Their Applications in Catalytic Semihydrogenation of Alkynes and Hydrogenation of Alkenes: Evidence for Metal-Ligand Cooperation.

The development of catalysts for environmentally benign organic transformations is a very active area of research. Most of the catalysts reported so far are based on transition-metal complexes. In recent years, examples of catalysis by main-group metal compounds have been reported. Herein, we report a series of magnesium pincer complexes, which were characterized by NMR and X-ray single-crystal diffraction. Reversible activation of H2 via aromatization/dearomatization metal–ligand cooperation was studied. Utilizing the obtained complexes, the unprecedented homogeneous main-group metal catalyzed semihydrogenation of alkynes and hydrogenation of alkenes were demonstrated under base-free conditions, affording Z-alkenes and alkanes as products, respectively, with excellent yields and selectivities. Control experiments and DFT studies reveal the involvement of metal–ligand cooperation in the hydrogenation reactions. This study not only provides a new approach for the semihydrogenation of alkynes and hydrogenation of alkenes catalyzed by magnesium but also offers opportunities for the hydrogenation of other compounds catalyzed by main-group metal complexes.

Comparative CO2 Hydrogenation Catalysis with MACHO-type Manganese Complexes

A pair of manganese complexes containing MACHO-type pincer ligands bearing a secondary amine, [HN{CH2CH2(PiPr2)}2]MnH(CO)2, which can participate in pathways involving metal–ligand cooperation (MLC), and a tertiary amine, [MeN{CH2CH2(PiPr2)}2]MnH(CO)2, which cannot participate in pathways involving MLC, are compared for the hydrogenation of CO2 to formate in the presence of a base. Lewis acid cocatalysts are crucial for increasing the activity of both catalysts, with [MeN{CH2CH2(PiPr2)}2]MnH(CO)2 reaching TONs of up to 18,300 and yields of up to 73% in the presence of lithium triflate. This productivity is far greater than for the MLC capable secondary amine MACHO-supported manganese catalyst. Preliminary mechanistic experiments indicate that CO2 insertion into the Mn–H of each catalyst affords a stable manganese formate complex. In situ NMR spectroscopy and comparative catalytic experiments are consistent with the intermediacy of these manganese formate complexes in the catalytic cycle, likely representing the catalyst resting states. Our findings suggest that the tertiary amine ligated system gives greater productivity due to a combination of longer catalyst lifetime and greater enhancement from Lewis acid additives.

Exploring the conversion mechanism of formaldehyde to CO2 and H2 catalyzed by bifunctional ruthenium catalysts: A DFT study

Bifunctional catalysts have a wide range of applications in chemical hydrogen storage. However, the versatile structure and complex influencing factors of catalysts still limit the current mechanistic understanding. Herein, a theoretical study based on density functional theory calculation is performed to illuminate the mechanistic preference of the conversion from formaldehyde to CO2 and H2 catalyzed by bifunctional ruthenium catalysts. The computational results indicate: (1) In contrast to the previously proposed mechanism, the catalyst is involved in the formaldehyde hydrolysis reaction and effectively reduces the activation free energy barrier. (2) Metal ligand cooperation mechanism is preferred instead of the metal-centred mechanism due to the stronger interaction between substrate and dual active sites on the bifunctional catalyst. (3) The catalyst with the OH group exhibits better catalytic activity compared with the NH group due to appropriate catalytic driving force, which is governed by the intrinsic electronic effects of the Lewis basic functional ligand. The pKa value can be used as a reliable descriptor to evaluate the catalytic activity of the functional ligand. Our study highlights the advantages of bifunctional catalysts in dehydrogenation-related reactions and proposes feasible strategies for the regulation of bifunctional catalyst activity, which is expected to provide new inspiration for future bifunctional catalyst design.

Generation and Aerobic Oxidative Catalysis of a Cu(II) Superoxo Complex Supported by a Redox-Active Ligand.

Cu systems feature prominently in aerobic oxidative catalysis in both biology and synthetic chemistry. Metal ligand cooperativity is a common theme in both areas as exemplified by galactose oxidase and by aminoxyl radicals in alcohol oxidations. This has motivated investigations into the aerobic chemistry of Cu and specifically the isolation and study of Cu-superoxo species that are invoked as key catalytic intermediates. While several examples of complexes that model biologically relevant Cu(II) superoxo intermediates have been reported, they are not typically competent aerobic catalysts. Here, we report a new Cu complex of the redox-active ligand tBu,TolDHP (2,5-bis((2-t-butylhydrazono)(p-tolyl)methyl)-pyrrole) that activates O2 to generate a catalytically active Cu(II)-superoxo complex via ligand-based electron transfer. Characterization using ultraviolet (UV)-visible spectroscopy, Raman isotope labeling studies, and Cu extended X-ray absorption fine structure (EXAFS) analysis confirms the assignment of an end-on κ1 superoxo complex. This Cu-O2 complex engages in a range of aerobic catalytic oxidations with substrates including alcohols and aldehydes. These results demonstrate that bioinspired Cu systems can not only model important bioinorganic intermediates but can also mediate and provide mechanistic insight into aerobic oxidative transformations.

Hydrogenation Involving Two Different Proton- and Hydride-Transferring Reagents through Metal–Ligand Cooperation: Mechanism and Scope

Hydrogenation Involving Two Different Proton- and Hydride-Transferring Reagents through Metal–Ligand Cooperation: Mechanism and Scope

Enantioselective Dearomative Cyclization Enabled by Asymmetric Cooperative Gold Catalysis

AbstractA gold(I)‐catalyzed enantioselective dearomatization is achieved via metal‐chiral ligand cooperation. A new and divergent synthesis of chiral bifunctional binaphthyl‐2‐ylphosphines is developed to allow rapid access to these ligands, which in turn facilitate the application of this chemistry to a broad substrate scope including 1‐naphthols, 2‐naphthols, and phenols. Enantiomeric excesses up to 98 % are achieved via selective acceleration of one enantiomer formation enabled by hydrogen bonding between substrate and ligand remote basic group. DFT calculations lend support to the cooperative catalysis and substantiate the reaction stereochemical outcomes.

Enantioselective Dearomative Cyclization Enabled by Asymmetric Cooperative Gold Catalysis.

A gold(I)-catalyzed enantioselective dearomatization is achieved via metal-chiral ligand cooperation. A new and divergent synthesis of chiral bifunctional binaphthyl-2-ylphosphines is developed to allow rapid access to these ligands, which in turn facilitate the application of this chemistry to a broad substrate scope including 1-naphthols, 2-naphthols, and phenols. Enantiomeric excesses up to 98 % are achieved via selective acceleration of one enantiomer formation enabled by hydrogen bonding between substrate and ligand remote basic group. DFT calculations lend support to the cooperative catalysis and substantiate the reaction stereochemical outcomes.

Unexpected role of two ortho-OH groups for the hydrogenation of CO2 to methanol catalyzed by Fe bipyridinol complexes

A density functional theory study of Fe-catalyzed hydrogenation of CO2 to methanol reveals an unexpected metal–ligand cooperation mechanism with two ortho-OH groups play key roles for the breaking of C–O and O–H bonds and formation of O–H…O hydrogen bonds. The formation of methanediol via hydride transfer from Fe to formic acid (4′ → TS6,7) is the rate-determining step with a total barrier of 30.8 kcal mol−1 in free energy. Furthermore, by replacing the two meta (R1) and two para (R2) hydrogen atoms in the bipyridinol ligand and the coordinated CN and CO with different functional groups, we built a series of stable iron complexes and computationally predicted their catalytic activities for hydrogenation of CO2 to methanol. Among all newly proposed iron complexes, 1t and 1u are promising catalyst candidates for hydrogenation of CO2 to methanol with rather low total free energy barriers of 26.6 and 28.8 kcal mol−1, respectively. The electrostatic potential map analysis indicates that stronger electron donating ligands on iron may lead to higher catalytic activities.

Cobalt Silylenes as Platforms for Catalytic Nitrene‐Group Transfer by Metal–Ligand Cooperation.

A cobalt silylene (Co=Si) linkage enables a distinct metal/ligand cooperative activation of an organic azide, where nitrene transfer occurs to and from the Co⋅⋅⋅Si linkage without ligand dissociation from the 18-electron cobalt center. This process utilizes the orthogonal binding affinities of the silicon and cobalt sites to avoid CO poisoning that would otherwise inhibit reactivity, leading to significantly improved catalytic isocyanate generation compared with related systems. The dual-site approach demonstrates the potential of metal/main-group bonds to access new and efficient catalytic pathways.

Cobalt Silylenes as Platforms for Catalytic Nitrene‐Group Transfer by Metal–Ligand Cooperation.

A powerful approach to cooperative group-transfer catalysis is demonstrated using the Co=Si bond of a cobalt silylene to provide two distinct sites for substrate activation. The orthogonal selectivity of the Co and Si centers enables efficient nitrene-group transfer to carbon monoxide by avoiding poisoning that would result from substrates competing for a single reactive site.

Single-Molecular Mn(I)-Complex-Catalyzed Tandem Double Dehydrogenation Cross-Coupling of (Amino)Alcohols under Solventless Conditions with the Liberation of H2 and H2O

Sustainable chemical production requires fundamentally new types of catalysts and catalytic technologies. The development of coherent and robust catalytic systems based on earth-abundant transition metals is essential but extremely challenging. Herein, we report the first report on a single Mn(I)-PNP catalyzed tandem C–C and C–N bond formation via double dehydrogenative coupling of amino alcohols with primary alcohols. The current method covers a wide range of substrates, including aryl, aliphatic, acyclic, and cyclic primary alcohols, as well as amino alcohols, to provide diverse N-heterocyclic compounds (pyridine and quinoline derivatives) in good to excellent yields (50 examples). The reaction proceeds under benign, solventless conditions with the liberation of molecular hydrogen and water as the only byproducts. Various control and labeling experiments and kinetic, nuclear magnetic resonance, and mechanistic studies suggest that the reaction operates via the acceptorless double dehydrogenative coupling pathway, selectively assimilating to provide desired N-heterocycles. Several selective bond activation/formation reactions occur sequentially via amine–amide metal–ligand cooperation.

Ruthenium-Catalyzed Dehydrogenative Functionalization of Alcohols to Pyrroles: A Comparison between Metal-Ligand Cooperative and Non-cooperative Approaches.

Herein, we report the synthesis and characterization of two ruthenium-based pincer-type catalysts, [1]X (X = Cl, PF6) and 2, containing two different tridentate pincer ligands, 2-pyrazolyl-(1,10-phenanthroline) (L1) and 2-arylazo-(1,10-phenanthroline) (L2a/2b, L2a = 2-(phenyldiazenyl)-1,10-phenanthroline; L2b = 2-((4-chlorophenyl)diazenyl)-1,10-phenanthroline), and their application in the synthesis of substituted pyrroles via dehydrogenative alcohol functionalization reactions. In catalyst [1]X (X = Cl, PF6), the tridentate scaffold 2-pyrazolyl-(1,10-phenanthroline) (L1) is apparently redox innocent, and all the redox events occur at the metal center, and the coordinated ligands remain as spectators. In contrast, in catalysts 2a and 2b, the coordinated azo-aromatic scaffolds are highly redox-active and known to participate actively during the dehydrogenation of alcohols. A comparison between the catalytic activities of these two catalysts was made, starting from the simple dehydrogenation of alcohols to further dehydrogenative functionalization of alcohols to various substituted pyrroles to understand the advantages/disadvantages of the metal-ligand cooperative approach. Various substituted pyrroles were prepared via dehydrogenative coupling of secondary alcohols and amino alcohols, and the N-substituted pyrroles were synthesized via dehydrogenative coupling of aromatic amines with cis-2-butene-1,4-diol and 2-butyne-1,4-diol, respectively. Several control reactions and spectroscopic experiments were performed to characterize the catalysts and establish the reaction mechanism.